One Size Fits All?

Is One Size Leptospirosis Vaccine Dose Really Right For All Dogs?

Ron Hines DVM PhD

Anaphylactic (Shock) Reactions In Your Dog  

 A Science-Based Vaccination Schedule For Your Dog    

Dog owner experiences with this problem  

This is a difficult article to read for most people who visit my website. It is long-winded and technical. If anything is unclear, you can send me an email and I’ll do my best to help you through it.

I receive a lot more vaccine reaction emails than I would wish to. Two dog owners recently wrote me to express their grief at loosing their dogs subsequent to having received leptospirosis vaccine boosters. Veterinarians have long known that lepto-containing vaccines appear the most likely to give unwanted and unanticipated vaccine reactions [ref1, ref2 ] )  It troubles me when grieving dog owners ask complicated questions that are difficult for me to answer. So I wrote this article for them. I hope it answers some of your questions too.

When I began writing this page, a good friend of mine in Connecticut had run into serious legal issues while trying to protect his client’s pets from excessively large or totally unnecessary booster vaccinations. (ref)   Too much compassion for animals can have legal consequences. Later that month, I saw an AVMA quote from a Department of Agriculture’s vaccine regulator describing vaccine manufacturers as his “clients”. How strange – I had thought that pet owners, pets and practicing veterinarians were the clients of the CVB (the USDA Center For Veterinary Biologicals) ? (ref) Another sign that the time had come to have a closer look at this whole sordid situation.

The last East Coast client’s dog with a severe vaccination reaction had received Merial’s Recombitek® 4LEPTO. So I called the Merial veterinarian’s hotline. The pleasant young veterinarian who answered seemed to know little more about the frequency of vaccine reactions than I did. The vaccine safety studies that the Merial website promos and product labels referred to and that she promised to send me never arrived. Another dog with a fatal vaccination reaction belonged to a US servicewoman stationed in Japan who had written me. It had received Merck’s Nobivac ® Lepto 4 vaccine . My attempts at obtaining vaccine reaction data on that product from Merck were equally unsuccessful.

So I called the veterinarian’s inquiry line at the USDA Center For Veterinary Biologics (CVB) in Ames, Iowa. Their Biologics Specialist, a PhD in Molecular Biology, was uninformative, condescending and moderately hostile. Not only would he not discuss vaccine reactions with me, he told me that all adverse events (bad reactions) reports that the CVB receives from the public and veterinarians alike become “proprietary” – property of the vaccine manufacturers and I was not allowed to see them. So I asked to view the initial safety studies submitted to the CVB when the vaccines were initially approved. He refused that as well and chuckled that any attempts I might make to obtain additional information under The Freedom of Information Act (ref) would be unsuccessful as well. He was wrong. (ref)

Dog owners like you are in a unique situation when it comes to your pet’s vaccine safety and efficacy. Although all human vaccines are reviewed for safety and efficacy by the FDA; all animal vaccines are supposed to be reviewed for their safety and efficacy by the US Department of agriculture under an archaic law, The Virus-Serum and Toxin Act of 1913. That law was enacted because of some worthless pig vaccines that came on the pork producers market. (ref) You can see any bad reaction reports on the vaccines you and your family receive anytime. The FDA posts all of them that they or the manufacturers receive online. But you are not allowed to see the same information when it comes to your dog or cat.

Over the years, the veterinary establishment (AVMA) has developed an inflexible, pyramidal structure – much like the old monarchies of Europe. Their official position is that vaccine dose has nothing to do with bad (“adverse events”) reactions. The one-size-fits-all vaccine dogma reigns supreme and it is considered blasphemy to question it. I have plenty of projects on my “to-do” list and wasn’t thrilled to have another. Besides, I am already considered by the AVMA to be a subversive. (ref)

First I decided to write to the most knowledgeable person I knew of regarding vaccines, Dr. Plotkin to ask him his thoughts. Dr. Plotkin replied  that my “perception that there were no studies that addressed the question [of proper dose size scaled to body weight] was correct”. He went on to write that most human beings at specific ages just do not differ enough in weight for those type of studies to have been a priority. He acknowledged that that most certainly was not the case in dogs.

What Happens After My Dog Receives A Leptospirosis-Containing Vaccination?

I sometimes use the word vaccine and antigen (really its active ingredient) interchangeably. When I say “antigen mass” I mean the amount of antigen in the vaccine dose. But although the primary ingredient in all vaccines are antigens, most vaccines contain other ingredient, either required in their manufacture (such as various blood and meat extracts,  BSA, etc. [ref] ) or things added to increase the product’s ability to stimulate your dog’s immune system (adjuvants ). They are not without risk. (ref)

As I write, there are 8 leptospirosis-containing vaccines on the market in the United States (rptref) All but one combine the leptospirosis part (a dead antigen) with attenuated (weakened) live virus antigens (=modified live virus or MLV) designed to protect your dog against a variety of other common canine diseases (=”multivalent” vaccines). How your dog’s body reacts to dead (inactivated) antigens like the leptospirosis part and how it reacts to the live MLV antigens are quite different. With killed products like lepto, all the antigen your dog is going to get is in the syringe. With MLV vaccine, the weakened virus grow within the dog producing much more antigen than was in the syringe. To gain any benefit from the lepto portion, their has to be a large amount of antigen give.

In the case of MLV vaccines, like those against distemper or parvovirus, only enough organisms (antigen mass) need be given to assure that they multiply in your pet’s body and that the resulting (very mild) infection produces protective antibodies and “immunological memory” that will guard your pet in the future. In the second type (killed antigen vaccines=bacterins) like leptospirosis, Lyme  or rabies vaccine, we count on the mass (the quantity) of dead antigens in the syringe to produce the antibodies and “immunological memory” that will protect your pet in the future. Immunity imparted by MLV vaccines is considerably better and lasts much longer that immunity given by killed products like lepto.

Within an hour or so of receiving the shot, the killed lepto antigens in the vaccine will be carried through your pet’s lymphatic vessels  to the dog’s  lymph nodes nearest the injection site. The courier cells that carry the antigens are called dendritic cells – sentinel guarding cells of your pet’s immune system that are scattered throughout its body. They are particularly common under the surface of your dog’s skin, nose, lungs and intestine – the places invading bacteria and virus are most likely to try to enter its body.

Dendritic cells deliver (“present”) the vaccine antigen to another type of lymph node cell, the virgin (“naive”) T-cells (CD4+ T cells), along with orders to begin dividing and to produce peptides and combine them with MHCII  molecules. The peptide-MHCII complexes will stimulate your pet’s CD4+ T cells to divide (proliferate) to their Th1 , activated form. Others will become cells (Tfh or T-folicle helper cells) that assist certain B-cells (plasma cells) in your pet’s lymph nodes in producing antibodies against the vaccine antigens that were injected. If this choreographed “dance of the cells” does not go precisely as ordered, your pet will not become immune or your pet will produce antibodies that are not in the best interests of its short term and/or long term health. (ref1, ref2)

Here is the critical problem:

If your smaller dog gets a whopping dose of leptospirosis antigen through a vaccination – more than its regional lymph nodes can process (opsonize) – what becomes of the excess?  Is the excess antigen toxic? With lepto, certainly so. Might it cause anaphylactic shock? Possibly, if the dog’s immune system was primed by a prior lepto vaccination or natural exposure. Does it actually decrease long term immunological memory? No one knows. Will this excess antigen affect the dogs liver, kidneys or other organs? Possibly so. (ref1, ref2, ref3) Vaccine manufacturers and the AVMA don’t want you to ask those questions. They are also not about to run the simple studies that would answer those questions or the more extensive ones that would scale leptospirosis vaccination dose size to your dog’s body weight.

Throughout the process, “memory cells” (B and types) are also created in dogs with normal immune systems – cells that will begin the antibody forming process again in a more rapid fashion if an antigen similar to the one in your pet’s vaccine ever enters its body again. Some of those cells live a very long time (10+ years, perhaps a lifetime). (ref1, ref2, rerf3) Those cells are the reason your dog will never become ill with parvo or distemper once a single effective vaccine dose against parvo and distemper gets properly processed by its immune system.  However, other antigens, like the antigens that leptospirosis produce (LPS  or surface lipopolysaccharides), do not produce nearly as good immunological memory.  Those are the ones that require your veterinarian to periodically “remind” the pet’s immune system with a booster vaccination. (ref) Those are all diseases that your dog or a human can catch more than one time. Running antibody titer tests tell you little or nothing about your dog’s long term immunological memory to resist a disease or the need for booster vaccinations. Human childhood vaccination studies have confirmed that the two processes operate through different mechanisms. (ref)

How Frequently Do Leptospirosis Vaccine Side Effects Occur And What Is In These Vaccines That Cause Them To Have So Many Side Effects?

A vaccine’s potential for undesirable side effects is sometimes called its potential for “reactogenicity”.

My calls and emails to the USDA Center for Biologics in Ames, IA and Merial were an attempt to get that answer for you. Neither would cooperate in providing the information I know that they have on file. The European veterinary regulatory agency was similarly tight-lipped about providing that data. In December of 2013, I managed to get some bad reaction reports from the USDA by filling a Freedom of Information Request. None of the reports they sent me were sufficiently detailed to be of value. In January, 2014, I received an email from the Center For Veterinary Biologics informing me that they planned to change their policy in the near future to require vaccine manufacturers to report all undesirable (adverse) vaccine reactions to them – as well as make that data easily accessible online to the public on the CVB website. As of mid 2019, they still have not done so.

Dog owners like you and veterinarians are at a disadvantage. The pharmaceutical companies fear transparency. They have an army of lobbyists in Washington to protect their interests; but there is no one there lobbying for you or your pet.  If one brand of vaccine causes more problems than another or if one vaccination method is safer than another is something they never intend to reveal to you.

In any case, there are major problems in drawing conclusions from Adverse Event Reports. Those are the letters that pet owners and veterinarians send – of their own volition – to vaccine manufacturers or the CVB. Experience in human medicine shows that only about 1% of human adverse events get reported to the FDA. (ref) The number that get reported to CVB likely only a fraction of 1%. (ref)

I believe that the leptospira’s own surface proteins in the vaccine (their LPS lipopolysaccharides antigens) have the potential to cause adverse reactions in dogs on their own accord. If ancillary ingredients in the vaccine were responsible, the problem would have been corrected by now. Lipopolysaccharides are reactogenic in their own right. (ref) Other ingredients in these vaccines – particularly when given in excess – have the potential to cause bad reactions too. (ref) But because of the anti-disclosure practices of the CVB and the vaccine manufacturers, I cannot tell you how much they contribute to the problem.

Is The Dynamics Of Every Bad Vaccine Reaction Pretty Much The Same?

No, things can go wrong in multiple ways.

First, all vaccine antigens have their own characteristics that govern how your pet’s immune system handles them. Some, like leptospirosis antigen are highly “reactogenic” (inclined to cause unwanted reactions) some are considerably less so.

Second, there are many places along the immunity road where the process can take a wrong turn and producing the wrong type of antibodies (IgE antibody-class switching, promiscuous antibodies, etc.)   IgE is the class of antibodies that are usually associated with allergy, hypersensitivity and anaphylactic shock. But in some cases, adverse reactions occur in the absence of circulating IgE antibody. The process is extremely complex and much has yet to be learned.

The likelihood of bad reactions in dogs increases with “booster” vaccinations because the dog’s memory cells (primed by the dog’s initial puppy shot series) are then taking part in the process. The focus points where these unwanted reactions occur also vary. In some dogs, their skin and underlying tissue is the primary focus point – those dogs develop hives, swelling and itching (sometimes with fever). These signs usually pass leaving no permanent damage. But they should be warning enough never to repeat those vaccinations. In other dogs, lung tissue is the central point of the reaction – when it is, their ability to breath is affected. In others, their cardiovascular system loses its ability to sustain vital functions. That can lead to circulatory collapse (=shock) so it is by far the most dangerous type of all.

Complicating our understanding is the fact that these are often fleeting, emergency situations where dynamics change from second to second. Some are certainly due to non-key components (bovine albumen, antibiotic additives like neomycin thickening and syringability agents such as gelatin, and adjuvants designed to aid in the antigen presentation process). (rptref) What percentage, I cannot say.

Many factors you might not consider can enter into the effectiveness of vaccines. Overweight children were found to respond poorly to DTP vaccinations. That problem was solved using longer needles (fat does not have an adequate lymph supply to get the vaccine’s antigens to the child’s lymph nodes efficiently). Perhaps similar things occur in chubby dogs. No one knows.

Can You Tell Me More About The Life Threatening Reactions – The Ones Called Anaphylaxis?

Your dog has a group of “first responder” immune system cells (mast cells ) designed to release “alarm chemicals” (cytokines  , histamine , etc.) when they detect foreign antigens the pet’s immune system has encountered in the past – a form of non-specific “chemical warfare”. Basophils in your dog’s blood perform similar functions. They wear a coat of plasma cell-generated IgE (on their surface FceRI  receptors) that was designed to be triggered by only one specific foreign antigen that your pet encountered some time in the past. Things exist in Nature for a reason – not just to cause problems. It is normal for humans and pets alike to produce these forms of antibody-coated mast cells and basophils; we are still unsure what all those normal functions are, but they are vital to your pet’s properly working immune system. (ref)  In any case, IgE “gone awry” usually comes up in discussions of all types of allergies – from a sneezy nose, allergic skin disease, fleabite sensitivity to life threatening anaphylactic shock.

The cytokines and histamines that these cells release cause blood vessels in the area of release to expand (dilate) and leak fluid (angioedema). When that is a whole-body occurrence, your dog or cat’s blood pressure can drop dangerously low and its lungs can become critically congested with leaked blood plasma (pulmonary edema ). You can read a less simplistic explanation here (ref)

Some cases are called “anaphylactoid” reactions. They are indistinguishable from true anaphylaxis in their appearance and effects and I cannot tell you which are most likely to occur subsequent to pet vaccinations. An adverse event occurring the first time a dog received a specific vaccine would most likely be anaphylactoid while one occurring after booster vaccinations, true anaphylaxis.  But there are other ways a pet could be primed for true anaphylaxis. Unlike most things your dog gets vaccinated for, there are over 200 species of leptospira. And of them, only 6 are known to cause disease in dogs. (ref) Damp, humid environments, particularly near water impoundments, are full of non-pathogenic leptospira (saprophytic leptospira). Perhaps association with them pre-sensitize certain dogs. When it was verified to be the pet’s first exposure to a leptospirosis-containing vaccine, it might be more appropriate to just call the bad reaction a cytokine storm.

Not every case of leptospirosis in dogs is detected. Many dogs recover naturally without their owners ever realizing the pet was ill. Some veterinarians believe that  those dogs could be more susceptible to anaphylactic reactions on their subsequent vaccinations when the vaccine contains leptospirosis strains (serovars) the dog was naturally exposed to in the past (ref)

Although I gave you the classical explanation for anaphylaxis, there are cases where the theory does not appear to hold up – crises occurring on the first exposure to a vaccine antigen and cases that occur in an obvious dose size-dependent manner. 

Is It True That All Size Dogs Should Be Given The Same Size Vaccine Dose Regardless Of Their Weight And Size? That Just Doesn’t Sound Logical To Me.

Veterinarians are taught to believe that in school because that notion is nurtured by the AVMA , the veterinary vaccine industry and their government regulators. You can read a typical response to a pet owner who brings a toy breed dog and a giant breed dog to their veterinarian for yearly vaccinations and questions why they both get the same dose  here.

However all of modern vaccine science indicates smaller dogs are likely to do better when their vaccine dose size is reduced. They may even have stronger, longer lasting immunity when their dose size is tailored to match their body weight and immune system needs.

I will have to reach far from your neighborhood dog and cat hospital into the Animal Kingdom to show you examples of why that has been found to be true. When I cross species lines, it is true that the size-versus-dose relationship could be questioned. At the least, consider them as proof of concept and keep in mind that the immune systems of all mammals are very similar in their basic function.

Almost all vaccines in use in humans today relied on cross-species tests when their effectiveness and safety were first established. The list I give you is a long one. But the point needed to be strongly made because the industry pushes back hard against it. Giving an amount of vaccine in proportion to body weight is called dose scaling or allometric scaling.  It doesn’t come up frequently across the spectrum of all vaccines because dogs are the only species on the planet whose adult body weight varies to such an extreme that it becomes important.

Rabies Vaccine

Like leptospirosis vaccines, many rabies vaccines are also killed antigen products that rely on the amount of antigen mass in the syringe to impart protective immunity to your pet.  Some years ago, the CDC worked out a procedure for vaccinating bats against rabies using dog rabies vaccine:
Take a gray wolf, probably similar to the progenitor of all dogs. An adult weighs about 36,000 grams. An Egyptian fruit bat weights about 125 grams and a Mexican free-tailed bat 11-14 grams. Is the same 1 ml dose of dog rabies vaccine required to immunize all of them effectively ? …. No. Fruit bats were successfully immunized with 0.1 ml of the dog vaccine and free-tail bats were successfully immunized with 0.05 ml. Read the studies here and here.   (The CDC considers ≥  0.5 IU/mL of antibody to be protective in all animals.) Rabbits (~4.8 kg) are successfully immunized against rabies with a 0.25 ml dose of dog rabies vaccine. (ref)
The One-Size-Dose-Fits-All theory that the vaccine manufactures the CVB and the AVMA preach certainly didn’t work there.

Ringling Bros. Circus elephants weight between 1,645 and 4,741 kg. It takes two 4ml doses of bovine rabies vaccine to immunize them against rabies. Even that massive dose was insufficient to reliably sustain  ≥  0.5 IU/mL  titers, (ref) The need for larger vaccine doses in heavy animals like elephants versus lighter weight animals has been known by zoo veterinarians for over 40 years. Since no commercial elephant vaccines exist, horse or cattle vaccines are given to elephants at 2-3 times the amount suggested for horses and cattle. (ref) The One-Size-Dose-Fits-All theory that the vaccine manufactures the CVB and the AVMA preach certainly doesn’t work there either.

Our Feathered Friends

Birds are not mammals. But birds get the flu too. When the veterinarians at the Rotterdam Zoo were concerned that their birds might catch it (avian influenza H7N1), they gave them a bird flu vaccine designed for chickens. The chicken dose was 0.5ml. They found that there was an inverse relationship between the bird’s weight and the protection the vaccine gave. So, subsequently, birds weighing 1.5kg or less received 0.25ml and birds weighing more than 1.5 kg received 0.5ml. However, even that dose was not sufficient to produce antibody protection in their heaviest birds – ostriches, rheas and cassowaries.  You can read about that here  , here  and here. Another failure of the One-Size-Dose-Fits-All theory.

How About When  My Kids Or I Go In For Our Vaccinations?

The most problematic vaccine that your children get are their DTP  shots. Anaphylactic reactions to DTP vaccinations are very rare – but fever, malaise and injection-site inflammation are quite common – particularly after the kids immune systems are sensitized by earlier DTP injections. (ref)  

Like leptospirosis , DTP vaccine is a killed antigen product, designed  to protect children against diphtheria, pertussis (whooping cough) and tetanus. In the case of DTP, the quantity of vaccine antigen (antigen mass) your children receives definitely does influence the frequency of adverse reactions. Studies have shown that children receiving half the suggested vaccine dose for their last vaccination develop adequate protection to these disease with significantly fewer side effects. (ref)  Every antigen in this 3-disease vaccine has unique qualities, when a somewhat reduced protection from a lower dose was noticed at all, it was for pertussis in preemies. (ref)  But over time, half-antigen mass pertussis protection equaled full dose pertussis protection. (ref1, ref2ref3) (Your kids need those shots. None of those childhood vaccinations are the cause of autism.)

It’s flu season. If you get Sanofi ’s Fluzone® vaccine, you will find that it has three different antigen mass suggestions. If you’re a mature adult, you will get 45 µg of combined HA antigens. Your child under 3 will get 22.5 µg of combined HA antigens and senior citizens will get 180 combined HA antigens because elderly immune systems are less efficient at producing antibodies against the flu. Those suggestions are because Sanofi ‘s clinical trials found that a One-Size-Dose-Fits-All approach did not work for this product either. (ref)

Americans are rarely vaccinated for tuberculosis. But in areas of the world where that vaccine (BCG) is routinely given, the dose for a small child is half the dose given to an older child or adult. (ref

What Can We Learn From Bioterrorism Research?

My best vet tech in Sarasota, FL move to the Washington D.C area. So I put her in touch with old friends at the NIH. She was quickly hired and emailed me that she was being immunized against anthrax – with a killed antigen product not unlike the leptospirosis vaccine.  But to test their anthrax vaccine for safety and efficacy, prior to its use in humans, the researchers used rhesus macaque monkeys.

Adult rhesus monkeys weight 5-7 lbs (2.3-3 kg). Pharmaceutical companies often use 120-150 pounds (54.5-68 kg) as an average adult human weight. The anthrax vaccine developers gave various groups of monkeys anthrax vaccine at various doses to see what protection it afforded before the monkeys were later infected with living anthrax.

In this small test, more monkeys survived anthrax when they had been immunized with half the human vaccine dose than the full human vaccine dose (100% survival vs 80% survival). Protocols were then modified so that today, all rhesus monkeys receive one-fifth the human dose. So too large a vaccine antigen dose might actually give your dog less protection against leptospirosis than a more refined dose based on your dog’s actual body weight. Read the article  here. Those results reminded me of an early experiment where smaller vaccine doses produced better immunity in monkeys than a larger one – in that case, to rabies vaccine. At the time, the authors theorized that the full human dose was too large for the smaller monkey’s immune system to effectively handle. (ref) Two more One-Size-Dose-Fits-All failures.

Vaccines In Development Often Begin In Mice

 NIH currently invests a great deal of effort looking for effective vaccines to prevent human AIDS. One promising approach is to link antigen components of the human immunodeficiency virus to a harmless adenovirus vector – something similar to Merial’s canarypox-vectored feline leukemia vaccine. Those researchers have found that the response in mice is better when the dose is reduced by 1-3 logs versus what they use in their human volunteers (a 1 log reduction is a ten times smaller antigen mass, a 3 log reduction is 1000 times smaller amount of antigen). Another confirmation that vaccine doses need to be scaled to the animal’s body weight.

What Can Ten Hamsters Tell Us?

They can tell us two things. They can tell us if a particular batch of leptospirosis vaccine is “up to snuff” ; that is if it meets quality control regulations and (if they could talk) they would tell you that an effective leptospirosis immunizing dose has to be adjusted to their body weight.

You probably thought that all sorts of sophisticated analytical machines were used to test the potency of your dog’s next dose of leptospirosis vaccine – right? Actually, each batch of leptospirosis vaccine relies on ten hamsters volunteered for a dangerous assignment.  Every year more than 32,000 hamsters do so. (ref)

These hamsters all weigh between 50 and 90 grams. (ref) Five of the hamsters are immunized with dog leptospirosis vaccine and five are not. Fifteen to 20 days later, all hamsters are given a potentially fatal dose of living leptospira. At lease four of the five unimmunized hamsters must die and four out of five vaccinated hamsters must live, for the vaccine batch to pass quality control. (ref)  Now according to the common wisdom, you would think that the hamsters would receive the same vaccine antigen dose suggested for dogs since the vaccine industry, the CVB and the AVMA all say that dose size doesn’t need to be scaled to body weight. However, that isn’t so. The immunized hamsters receive 1/40th of the recommended dog dose. Testing procedures for European dog leptospirosis vaccines are essentially the same as in the USA. (ref)

Hamster batch-testing does not tell you if one batch of vaccine is more reactogenic than another. For that, you would need something like a post-vaccination febrile (fever) test in dogs. I do not know if they bother to run them. But if they did, one could choose the least reactogenic brand of leptospirosis vaccine, should you choose to vaccinate your dog against leptospirosis.

I can’t tell dog owners like you or or veterinarians to scale their dog’s leptospirosis vaccine dose size to their pet’s body weight. Today, that is illegal. Until we have hard data release (if ever) that will be a decision that you and your personal veterinarian have to make. My opinion is that pets need just enough vaccine antigen to prime their individual lymph node memory cells – no more and no less. I hunted for weeks for an article that showed that the mass of those lymphoid cells in the body was proportional to a dog’s body weight but could find nothing one way or the other. The lymphatic system is an organ just like any other organ in your dog’s body – pancreas, liver, etc – and organ weight (mass) of all the others is proportional to their body size. Experimenting with vaccine dose-to-body weight relationships ought to be done within the confines of a veterinary college, the CVB or a licensed vaccine manufacturer – not forced to be done by practicing veterinarians like Dr. Robb or myself out of concern for their patient’s welfare. It is long overdue that those studies be done and that the instructions that come with the vaccines be modified accordingly.

Veterinarians in Japan feel the same way I do and have gone much farther in doing the research that we US veterinarians, the CVB and vaccine manufacturers have refused to do and the AVMA has failed to suggest. (ref) My take on the situation is that nothing I present here is news to the world’s dog vaccine industry. Faced with the extreme variation in the weight of our canine pets, these manufacturers and their regulators  had a decision to make. They could perform expensive trials to determine the correct (optimal) dose for various size and age dogs or produce one vaccine (by upping the antigen mass) that would protect the largest conceivable dog that would be given their product – although it would be more prone to cause severe reactions in smaller dogs now and then. They elected to take the second less expensive option and hoped no one noticed. However, that meant that smaller dogs would be vastly overdosed.

Is The Chance Of A Bad Reaction To A Vaccine A Simple Matter Of The Size Of The Dose and The Weight Of My Dog?


They are not simple dose/body weight equations (ie more dose = more reaction). They are related in a much more complicated non-linear way  and can occur over a wide range of doses. Another non-linear event is the weather. If you get up for work and find an overcast sky, you are more likely to take your umbrella with you because you anticipate the possibility of rain. It may rain and it may not rain – but you know the chances are greater than on a sunny day.

Well, Presumed Experts Know That Anaphylactic Reactions Are An All-Or-Nothing Event – So It Wouldn’t Make A Bad Reaction Any Less Likely If My Pet Got A Smaller Vaccine Dose – Right?


First, we do not know the true nature of post-vaccination reactions in dogs. They may be formal anaphylactic events that follow traditional explanations, or they may be anaphylactoid reactions that do not. Most likely many different types of bad reactions are lumped together in one bundle. 

Regarding anaphylaxis, it is true that there is a triggering dose (a threshold dose) that will cause reactions. In very sensitive pets, those whose mast cells are highly primed, it can be so small an antigen dose that it could be described as “any dose”. But that is not – strictly speaking – correct. Some believe that the greater the dose, the more likely those events are to occur and, possibly, the more violent they will be. Those dynamics of anaphylaxis are rarely studies. But it was examined with regard to anaphylaxis-triggering antigens such as peanuts that enter through the digestive system. (ref)  The graph from that article below, shows that in those author’s review the larger the dose exposure to those antigens was, the more likely an allergic or anaphylactic event was to occur. Click on the graph to enlarge it.


The Center For Veterinary Biologics (CVB)

When you receive a vaccination, the folks at the FDA’s (CBER) unit in White Oak, MD  look out  for your safety.  The CBER had a key professional staff of about 179 individuals in 2012. (ref) Its 2018 budget was $358 million dollars. (ref) However, your pet’s are not as lucky. All vaccines intended for animals are approved and supposedly monitored by the US Department of Agriculture’s Center For Veterinary Biologics in Ames, Iowa. The CVB had a professional staff of less than 39 individuals in 2013. (ref) It’s 2018 budget was only $16 million dollars – supplemented by hefty fees collected from the vaccine manufacturers themselves (never a good thing). (ref) The average starting salary for an FDA/CBER employee was estimated to be $91,000 in 2013. The average starting salary for a USDA/CVB employee was estimated to be $49,000 in 2013. Is there any wonder why the CBER does a better job of protecting you than the CVB does in protecting your dog and cat?

The CVB  that approves and monitor’s your pet’s vaccines is staffed by well meaning, honest people. But their current employment and hope of future advancement depends, in part, on staying in the good graces of the vaccine companies that fund them and their lobbyists in Washington who lobby intensely for those companies interests. Situations like that are ripe for gaming and misuse. Even the mighty FDA itself has to deal with it. (ref)

The FDA and USDA also have completely different philosophies when it comes to vaccine safety. The USDA/CVB’s focus has always been on agriculture where a cow’s value is a fixed and moderate amount, emotional attachment to the animal is minimal and a higher degree of adverse events is deemed acceptable (ref)


Every fall, the powerful  lobbying group for veterinary vaccine manufacturers, the AVBC (ref) , descends on Ames, Iowa like crows at corn harvest. It is highly unrealistic to expect the little group of Ames, Iowa mid-westerners at the CVB – no matter how dedicated and well meaning they might be – to protect the interests of pet owners like you across the Nation when faced with a  multi billion dollar veterinary drug industry intent on maximizing profits ($18 billion in 2017). They hear from plenty of lobbyists and industry spokesmen, but they don’t get many letters of thanks or protection from dog owners like you. As things now stand, the CVB has been reduced to a lady’s auxiliary to the veterinary vaccine industry. (ref)  

Inappropriate Selection Of Test  Dogs

The test animals, used to develop leptospirosis vaccines are too young to accurately reflect  the dynamics of the vaccine when it is administered to the older dogs that will constitute the majority of future patients. As an example, the MSD (aka Merck) leptospirosis vaccine marketed in Europe, Nobivac®DHPPi, was tested in beagle puppies that were only 6-10 weeks old. (ref)  Very few practicing veterinarians would inject leptospirosis-containing vaccines into a puppy that young. The immune system of a 6-10 week old puppy is too immature to be indicative of what occurs when an older dog receives the vaccine. The likelihood of reaction is worst in the middle years when several yearly injections have already primed the mast cell hypersensitivity (allergic reaction) system. At least with the strains of leptospirosis that Merck tested in Boxmeer, there is considerable room for downward antigen dose adjustment – one quarter the recommended vaccine dose gave adequate protection to their beagle dogs. (ref)  

Neither the CVB nor Merial would tell me the breed, let alone the weight, of the dogs used in CVB approval testing (although the French contingency of Merial used 8-16 week old beagles to test their Eurican1L canine leptospirosis vaccine. (ref)

Deceptive Vaccine Marketing Techniques

Most veterinarians (and informed pet owners) would assume that a vaccine with the name of Recombitek® 4 Lepto, marketed by Merial, would be a recombinant vaccine. Recombinant, subunit vaccines are those in which genes to produce the desired bacterial antigen have been grafted into a harmless organism – like yeast for increased purity and reduce bad event potential. For example, that is the technology that most human hepatitis B vaccine use. (ref) Even Merial press releases stated “Merial’s RECOMBITEK® family of canine vaccines have been developed with recombinant technology” (ref)

The pleasant veterinarian I spoke to on the Merial veterinarian’s hot line would not give me a straight answer when I asked if  Recombiteck was a recombinant vaccine. But a renown veterinary school professor kind enough to answer my email confirmed that it is not a recombinant vaccine. 

Are There Factors Other Than Dose Size That Could Make My Dog More Susceptible To A

Vaccine Reaction?

Most certainly so. 

Genetics, environment, nutrition and lifestyle all factor into the probability of bad vaccination events. In my opinion, breed genetics are highest on the list since they are known to have strong influences on immune system errors like skin and drug allergies. (ref1, ref2, ref3, ref4) The best thing a veterinarian like me can tell you is to try to change the things you and your veterinarian can change and hope we have lessened that probability of a reaction. (ref)

Can You Propose Ways That Too Large A Dose Of Leptospirosis Vaccine Might Increase The Likelihood Of Side Effects – What Do The World Experts Say?

I posed the question of best vaccine dose size/ to body weight to some of the world’s leading vaccine immunologists. Read their replies here.

The accepted veterinary pharmaceutical company/AVMA line is “ the cause of vaccine reactions is multifactorial” (that’s doublespeak for “we know these reactions occur, but we have no idea what the specific causes are”) “These are just a random act of nature – like being struck by lightening.

Reduced to the simplest of analogies, the immune process in your pet is similar to the performance of a dance troupe – a well choreographed performance between dendritic cell ladies adorned in IgE antigen costumes cavorting with their T-cell gentlemen – while memory B cells keep a record the performance to play it again  at some later date.  When excessive amounts of vaccine antigens are added, the situation can go out of control – to a point where inappropriate antibodies (class switching) and memory cells are produced in a chaotic manner. 

Rather than that fanciful explanation, you can read about the true processes that occur here: (ref1, ref2, ref3, ref4)

Anergy And Antigen Overload

Even when an excessive vaccine antigen dose does not cause an immediate vaccine reaction in your dog, it can have later negative consequences. Vaccine antigen given in excess of the pet’s lymph node requirements can actually produce a lower, less specific immunity to a disease like leptospirosis than antigen given in optimal amounts for the pet’s body weight. Perhaps something like that was in play with the CDC’s rhesus monkeys I mentioned earlier. Similar things occur when too large a dose of BCG vaccine is given to laboratory animals. (ref)   A similar phenomenon is what dermatologists take advantage of when they give you or your dog desensitization injections. They attempt to shift antibody response from Th2 to Th1 immune system cells. Excessive vaccine antigen is also known to reduce the “affinity” (specificity) of the antibodies produced. Being less specific, these rogue antibodies when coated on mast cells and basophils might trigger cytokine storms to antigens they encounter that have nothing to do with leptospirosis.

Are You One Of Those Anti-vaccination-Fixated Or Conspiracy Guys?

I am not at all against vaccines and vaccination.  Our dogs and cats need them – but in the right amounts and at the right times in their lives – to protect them from the serious diseases they are likely to encounter in the future. (rptref) Although I am disappointed in the USDA, I do not have an axe to grind with them, vaccine manufacturers or the institutionalized veterinary community. Vaccines and antibiotics are the two greatest health discoveries of the modern age. I just believe that we owe it to our dogs and cats to administer vaccines in accordance with current medical knowledge and that old practices need to be periodically reviewed in light of advances in our understanding of immunology. I also believe that the pursuit of money has replaced honesty in too many facets of my profession and American society in general.

What Can I Do To Minimize My Dog’s Risk When Time Comes For Its Booster Vaccinations?

The first thing you can do is to avoid succumbing to pressure to agree to vaccinations that are unnecessary. The current dynamics of veterinary medicine heavily encourage over-vaccination. Vaccination recommendations are never made in a vacuum. Veterinarians are caught in an economic squeeze: AVMA policies encourage an over-abundance of new graduates with low starting salaries – barely enough to pay off their sizable college loans. Candy bar corporations squeeze out or convert idealistic young vets who are less motivated by economics. CPAs in these veterinary hospital conglomerates closely scrutinize their average client revenue stream.

On line pet medication suppliers compete for your veterinarian’s pet medication revenues.

Vaccination buses cruse the Country indiscriminately pushing their vaccine wares. Endless advertising by vaccine manufacturers bombard veterinarians every day. Vaccine-related revenue is the easiest revenue we veterinarians earn – it and dispensed medications subsidizes many of the other services your dog depends upon. You can read about some of those pressures here. Vaccine manufacturers have no incentive to provide veterinarians or pet owners with information that would cause them to buy less of their vaccine products, neither does the CVB, academia which relies on vaccine company grants or veterinary institutional hierarchies.

I prefer not give multivalent (prevents more than one disease) vaccines to your dog when single disease products are available. Let your dog’s immune system focus on one antigen at a time when that is an option. There is no beneficial effect in giving combination vaccines and there can be detrimental effects – particularly when they contain known reactogenic ingredients such as leptospirosis antigens. The only benefit of 4-way and 5-way vaccines is convenience. Besides, if your dog gets multiple disease (polyvalent/multivalent) products and has a reaction, you won’t know which of the disease ingredients was the cause of it. The same goes for giving a rabies shot and other shots during the same office visit.

Those multiple (4-way, 5-way etc.) vaccines that contain leptospirosis as one of their ingredients  have the potential to cause immunosupression whereby less protection is given against multiple diseases. (ref)

It can be confusing to pet owners, some companies use the term “4-way” to describe vaccines, containing only leptospirosis but with ingredients from the four different common strains (serovars ) of the organism.

Do not begin your pet’s vaccinations at too young an age. Catching these disease requires exposure. Consider just not exposing your dog to those diseases by avoiding doggy parks, grooming salons and places where dogs congregate until the pet is at least 12-14 weeks old before starting vaccinations. When exposure can be avoided, give your pups immune system time to mature.

Be very cautious about vaccinating pets with chronic or acute health conditions. Nothing upsets me more that learning of a pet that was taken to an animal hospital for a medical problem only to leave with vaccine boosters. Also be extra cautious if littermates, parents or dogs in your pet’s family tree have ever had vaccine reactions or hives subsequent to vaccinations. If your dog has a vaccine reaction of any sort, write and store the information as to the type of vaccine and brand. Avoid those brands in the future and consider if the possible benefits of future vaccinations really outweigh the risks (in the future, there might even be other anti-IgE options for high-risk dogs). (ref)

Read the advice of a veterinarian who has spent considerable time considering this problem: here.

If you are concerned about vaccine risk and over-vaccination, do not use the services of mobile or periodically held “vaccine clinics”. They tend to be overly positive about the need for frequent vaccination and when serious vaccine reactions occur, they rarely have the specialized staff and emergency equipment on hand to treat them.

Remember that your dog is not protected the moment it receives its vaccination. It takes up to several weeks for the full protective effect of vaccines to develop. In one study, it was 21 days after the first lepto vaccination before that the dog’s antibodies began to rise. Protective antibodies did not reached their highest level until 6 weeks after the second injection. (ref) That is the fallacy of requiring things like a kennel cough vaccination the day before your dog enters a commercial boarding facility.

Are There Less Obvious Risks?

There might be other, less thought of, risks in unnecessarily exposing your dog or cat to vaccine antigens beyond the amount that is required to safely immunize it or in administering vaccines too frequently. Those dangers might exact a toll in ways that are more subtle than the obvious vaccine reactions I wrote about.  Antigen exposure is now thought to encourage many forms of autoimmune disease. (ref) Pet-owner response to this article and data I have obtained from the CVB make me quite concerned that leptospirosis-containing vaccines trigger autoimmune phenomena considerably more frequently than acknowledged by the pharmaceutical industry. Antigens, and the helper chemicals they contain (adjuvants), are not all that selective in the immune processes they encourage. Occasionally, a case of mistaken identity occurs and the body immunizes itself against itself (=autoimmunity). (ref) Perhaps that is what occurred in these three dogs. But considerably more complex (“foggy”) reactions are also possible:

I mentioned earlier that antibodies produced by vaccines can be “promiscuous”, that is, react with more than one perceived “invader”. We know from a 2012 study that leptospirosis vaccine antigen can do that. Cattle vaccinated against leptospirosis can have false-positive reactions for another disease (brucellosis ). (ref) Veterinarians do not know if similar cross-reactions occur in dogs. Leptospira is a spirochaete ; so is the  Lyme disease organism. How things like the in-office “Snap” tests used to diagnose Lyme and other such diseases might be affected by leptospirosis vaccinations (particularly when excessive amounts of vaccine are given to small dogs) is unknown. There is also a long-held suspicion that over-administration of vaccine antigens also takes a toll on the kidneys (ref)

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